Breast cancer research and treatment, 2010-01, Vol.119 (2), p.463-474
2010
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- Autor(en) / Beteiligte
- Titel
- Genetic polymorphisms in phase I and phase II enzymes and breast cancer risk associated with menopausal hormone therapy in postmenopausal women
- Ist Teil von
- Breast cancer research and treatment, 2010-01, Vol.119 (2), p.463-474
- Ort / Verlag
- Boston: Springer US
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Recent findings indicate a greater risk of postmenopausal breast cancer with estrogen–progestagen therapy than estrogen monotherapy, and more so for current than past use. Few studies have examined individual genetic susceptibility to the effects of menopausal hormone therapy. We used two population-based case-control studies with 3,155 postmenopausal breast cancer patients and 5,496 controls to evaluate modification of breast cancer risk associated with duration of hormone use by genes involved in hormone metabolism and detoxification. Twenty-eight polymorphisms in eight genes of phase I ( CYP1A1 , CYP1A2 , CYP1B1 , CYP2C9 , CYP2C19 , CYP3A4 , CYP3A5 , CYP3A7 ) and nine genes of phase II enzymes ( COMT , GSTM1 , GSTM3 , GSTP1 , GSTT1 , SULT1A1 , UGT1A1 , UGT1A6 , UGT2B7 ) were genotyped. The risk associated with duration of use of combined estrogen–progestagen therapy was significantly modified by genetic polymorphisms located in CYP1B1, GSTP1 , and GSTT1 . In homozygote carriers of the CYP1B1 _142_G and the CYP1B1 _355 _T variant alleles, adjusted odds ratios (OR) per year of use were 1.06 (95% confidence interval (CI) = 1.02–1.09) and 1.06 (95% CI = 1.03–1.09), respectively, compared with 1.02 (95% CI = 1.01–1.03) in non-carriers of either polymorphism ( p interaction = 0.01). Carriers of the functional GSTT1 allele and the GSTP1 _341_T allele were at significantly higher risks associated with hormone use compared with non-carriers ( p interaction = 0.0001 and 0.02). CYP1A1 _2452_C>A significantly reduced the risk associated with duration of use of estrogen monotherapy ( p interaction = 0.01). The finding regarding GSTT1 was still statistically significant after corrections for multiple comparisons. Postmenopausal breast cancer risk associated with hormone therapy may be modified by genetically determined variations in phase I and II enzymes involved in steroid hormone metabolism.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0167-6806eISSN: 1573-7217DOI: 10.1007/s10549-009-0407-0Titel-ID: cdi_proquest_miscellaneous_733687641
- Format
- –
- Schlagworte
- Aged, Biological and medical sciences, Breast cancer, Breast Neoplasms - chemically induced, Breast Neoplasms - enzymology, Breast Neoplasms - epidemiology, Breast Neoplasms - etiology, Breast Neoplasms - genetics, Cancer research, Cancer therapies, Case-Control Studies, Cytochrome P-450, Enzymes, Epidemiology, Estrogen, Estrogen Replacement Therapy - adverse effects, Estrogens - adverse effects, Estrogens - metabolism, Female, Gene Expression Regulation, Enzymologic, Gene Frequency, Genes, Genetic aspects, Genetic Predisposition to Disease, Germany - epidemiology, Glutathione transferase, Gynecology. Andrology. Obstetrics, Haplotypes, Health aspects, Hormone replacement therapy, Hormone therapy, Humans, Logistic Models, Mammary gland diseases, Medical sciences, Medicine, Medicine & Public Health, Menopause, Metabolic Detoxication, Phase I - genetics, Metabolic Detoxication, Phase II - genetics, Metabolism, Middle Aged, Odds Ratio, Oncology, Physiological aspects, Polymorphism, Polymorphism, Genetic, Postmenopausal women, Postmenopause, Progestins - adverse effects, Progestins - metabolism, Risk Assessment, Risk Factors, Tumors